The primary objective of the Pathology, Imaging and Flow Cytometry Core is to provide accurate phenotypic characterization of pulmonary vascular remodeling and inflammation in relevant models of PH. To accomplish these goals, we integrate high quality tissue processing, immunohistochemistry, and stereology with flow cytometry (FACS) to inform on the participation of inflammatory and structural cells in pulmonary hypertension in all three projects. To accomplish these goals, the following specific Aims are proposed: Specific Aim 1: To provide qualitative and quantitative assessment of pulmonary vascular remodeling in lungs of cows, rats, and mice in Projects 1-3. We propose 4 specific tasks to support this specific aim, which include: planning of experiments (task 1), collection, processing, and phenotyping experimental lungs (task 2), morphology and stereology of pulmonary vascular remodeling (task 4), and integration of morphological data with specific project goals and aims (task 9). Specific Aim 2: To determine expression patterns and abundance of candidate molecules investigated in experimental lungs. We propose 5 specific tasks to support this specific aim, which include planning of experiments (task 1), tissue processing (task 2), morphology and stereology (task 3), laser capture microdissection (LCM; task 7), flow activated cell sorting (FACS) (task 8), and integration of morphological data with specific project goals and aims (task 9). Specific Aim 3: To obtain high quality mRNA and DNA from specific pulmonary vascular structures and lesions from animals manipulated in Projects 1-3. We propose 5 specific tasks to support this specific aim, which include planning of experiments (task 1), tissue processing (task 2), LCM (task 7), and FACS (task 8), and integration of morphological data with specific project goals and aims (task 9). Specific Aim 4: To translate the key expression findings in Specific Aim 2 to human control and PAH lungs. We propose six specific tasks to support the specific aim, which include planning of experiments (task 1), tissue processing (task 2), human tissue studies (with Core B) (task 3), morphology and stereology (task 4), LCM (task 7), and integration of morphological data with specific project goals and aims (task 9). Foremost in accomplishing these goals is the scientific expertise within the leadership of the core. Core C is led by of Drs. Rubin M. Tuder, an experimental and practicing pulmonary pathologist with major expertise in pathology and pathobiology of pulmonary hypertension, William Jansen and Phil Simonian, who have extensive expertise in lung inflammation and macrophage biology. The novelty of the Core C lies on the unique resources, unmatched expertise, and overall experimental breadth, allowing for the integration and human translation pertaining to all three projects. PHS 398/2590 (Rev. 09/04) Page Continuation Format Page